Asymmetric catalysis is the most efficient method for the generation of products with high enantiomeric purity, as the asymmetry of the catalyst is multiplied many times over in the generation of the chiral product. These chiral products have found numerous applications as building blocks for single enantiomer pharmaceuticals as well as in some agrochemicals. The asymmetric catalysts employed may be enzymatic or synthetic in nature. The latter types of catalyst have much greater promise than the former due to much greater latitude of applicable reaction types. Synthetic asymmetric catalysts are usually composed of a metal reaction center surrounded by one or more organic ligands. The ligands usually are generated in high enantiomeric purity, and are the agents inducing the asymmetry. These ligands are, in general, difficult to make and therefore expensive. A notable exception are the chiral phosphine-aminophosphine ligands based on a phosphine-amine backbone described by Boaz et al., U.S. Pat. No. 6,590,115. These phosphine-aminophosphine compounds are useful as metal complexes for asymmetric catalysis and are readily prepared and air-stable.
Monodentate phosphoramidite ligands useful for asymmetric catalysis have been reported by de Vries, et al., Angew. Chem. Int. Ed. Engl. 1996, 35, 2374-2376; Malda, et al., Org. Lett. 2001, 3, 1169-1171; Alexakis, et al., J. Am. Chem. Soc. 2002, 124, 5262-5263; Pena, et al., J. Am. Chem. Soc. 2002, 124, 14552-14553; Ohmura, et al., J. Am. Chem. Soc. 2002, 124, 15164-15165; Urbaneja, et al., Tetrahedron Lett. 2002, 43, 7887-7890; Jia, et al., Tetrahedron Lett. 2002, 43, 5541-5544; Zeng, et al., Tetrahedron:Asymm. 2002, 13, 115-117; Choi, et al., Tetrahedron: Asymm. 2002, 13, 801-804; Li, et al., Tetrahedron:Asymm. 2003, 14, 2687-2691; Boiteau, et al., Org. Leff. 2003, 5, 681-684; Lopez, et al., J. Am. Chem. Soc. 2003, 125, 3426-3427; and Zhour, et al., J. Org. Chem. 2003, 68, 1582-1584.). These monodentate ligands have a single ligating group and have demonstrated moderate to high enantioselecitivity for a variety of asymmetric catalytic reactions including asymmetric hydrogenations. The monodentate ligands are, in general, prepared by reacting a diol with phosphorus trichloride followed by reaction with an amine (de Vries, et al., Angew. Chem. Int. Ed. Engl. 1996, 35, 2374-2376). Alternatively, the preparation of these types of ligands by the reaction of phosphorus trichloride with a preformed lithium amide (prepared from the amine and n-butyllithium) has been reported by Choi, et al., Tetrahedron:Asymm. 2002, 13, 801-804. There have been no reports of phosphine-phosphoramidite compounds prepared on a phosphine-amine backbone.